Renal: GN Flashcards
Define what the triad of nephrotic syndrome are [3]
A triad of the following:
1. Proteinuria (> 3g/24hr) causing
2. Hypoalbuminaemia (< 30g/L) and
3. Oedema
Define glomerulonephritis [1]
GN denotes glomerular injury and applies to a group of diseases that are generally, but not always, characterised by inflammatory changes in the glomerular capillaries and the glomerular basement membrane (GBM).
GN describes the pathology that occurs in various diseases rather than being a disease
Which are the diseases that cause glomerulonephritis? [5]
- Membranous nephropathy
- Post streptococcus nephropathy
- Focal segmental glomerulosclerosis
- IgA nephropathy
- Goodpasture’s disease
Which of the following is the most common cause of primary GN?
- Membranous nephropathy
- Minimal change disease
- Focal segmental glomerulosclerosis
- IgA nephropathy
- Goodpasture’s disease
Which of the following is the most common cause of primary GN?
- Membranous nephropathy
- Minimal change disease
- Focal segmental glomerulosclerosis
IgA nephropathy - Goodpasture’s disease
What symptoms are usually seen in glomerulonephritis? [4]
Haematuria (blood in the urine), which can be microscopic (not visible) or macroscopic (visible)
Oliguria (significantly reduced urine output)
Proteinuria (protein in the urine), but less than 3g per 24 hours (higher protein suggests nephrotic syndrome)
Fluid retention
What level of proteinuria would indicate nephrotic syndrome? [1]
What level of serum albumin would indicate nephrotic syndrome? [1]
Proteinuria: more than 3g per 24 hours
Low serum albumin: less than 25g per litre
Describe the clinical presentation of a patient with nephrotic syndrome [10]
- Oedema (peripheral and facial)
- Proteinuria (>3g/24hrs)
- Hypercholesterolaemia
- Hypoalbiminaemia
- Hypertension (caused by reduced eGFR and salt & water retention)
- Haematuria
- Frothy urine
- Fatigue
- Recurrent infections (immune dysfunction)
- A / V thrombosis (hypercoagulability)
- Xanthelasma (cholesterol deposit near eyelid)
- Leukonychia
Describe risk factors for GN [6]
- Group A Streptococcus pyogenes
- Respiratory infections
- GI infections
- Hep B
- Hep C
- Infective endocarditis
- HIV
- SLE
- Lung & Colorectal cancer
What is the difference between nephritic syndrome and nephrotic syndrome? [2]
What are the classic signs of each? [4 x 2]
Both are clinical syndromes that are at opposite ends of a spectrum of clinical presentations
Nephrotic syndrome (GN):
* When the basement membrane in the glomerulus becomes highly permeable resulting in proteinuria & involves
* Proteinuria (more than 3g per 24 hours)
* Hypoalbuminaemia / low serum albumin (less than 25g per litre)
* Peripheral oedema
* Hypercholesterolaemia
* Nephritic syndrome:
* General term for the inflammation of the kidneys; descriptive and not a diagnosis.
Nephritic syndrome:
is a clinical presentation, and patients with nephritic syndrome may be diagnosed with renal diseases such as glomerulonephritis (a pathological diagnosis made after biopsy), and maybe rapidly progressive glomerulonephritis (RPGN) in which a patient has rapid fall in renal function (RPGN is a subset of glomerulonephritis).
A nephritic syndrome is a constellation of symptoms:
* Haematuria (blood in the urine), which can be microscopic (not visible) or macroscopic (visible)
* Oliguria (significantly reduced urine output)
* Proteinuria (protein in the urine), but less than 3g per 24 hours (higher protein suggests nephrotic syndrome)
* Fluid retention
Describe the investigations would conduct for nephrotic syndrome? [7]
- Urinalysis: haematuria, proteinuria, dysmorphic rbc, leukocytes
- Protein:Creatinine ratio (PCR): >300mg/mmol
- Microscopy: investigate infections
- FBC: normocytic normochromic anemia is a feature of several systemic diseases with GN
- Lipid profile: hyperlipidaemia
- U&Es
- LFTs: hypoalbuminaemia; normal/elevated creatinine; elevated liver enzymes
- Ultrasound of kidneys
What is the most common cause of nephrotic syndrome in children? [1]
Minimal change disease
What are the top causes of nephrotic syndrome in adults? [2]
Membranous nephropathy
Focal segemental glomerulosclerosis
In the spectrum of glomular diseases, which are more:
Nephritic glomerulonephritis? [4]
Nephrotic glomerulonephritis? [3]
Nephritic glomerulonephritis:
- IgA nepropathy
- Post-strep GN
- Goodpastures
- Rapidly progessive GN
Nephrotic glomerulonephritis:
- Minimal change disease
- Membranous nephropathy
- Focal segemental glomerulosclerosis
Describe the pathophysiology of minimal change disease [4]
Podocyte injury: Diffuse effacement of the podocyte foot processes (without significant immune complex deposition or thickening of basement membrane).
As a result, glomerular filtration barrier becomes more permeable to proteins, particularly albumin, leading to nephrotic level proteinuria.
T-cell and cytokine mediated damage to the GBM cause polyanion loss. The resultant reduction of electrostatic charge causes increased glomerular permeability to serum albumin
The reduction in glomerular filtration barrier selectivity and the compensatory increase in glomerular filtration rate may contribute to glomerular hyperfiltration and cause CKD
The majority of cases of MCD are idiopathic, but in around 10-20% of cases, the cause is WHAT? [3]
· Drugs: NSAIDs, rifampicin
· Hodgkin’s lymphoma, thymoma
· Infectious mononucleosis
Describe the histological findings of MCD [1]
What type of microscopy do you use? [1]
Light microscopy is near identical to a normal glomerulus.
Electron microscopy: get effacement of the podocytes (only positive finding on histology for a patient with minimal change)
Describe the features of MCD [3]
- Features of nephrotic syndrome
- Normotension (HTN is rare)
- Highly selective proteinuria (i.e. only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus
Definitive diagnosis for MCD? [1]
Biospy and histology
Describe the management of MCD [2]
- Majority (80%) are steroid responsive: prednisolone
- Cyclophosphamide next step for steroid resistant
Define focal segmental glomerulosclerosis [1]
Focal segmental glomerulosclerosis (FSGS) is a chronic pathological process caused by injury to podocytes in the renal glomeruli, where sclerosis occurs in at least one part of the glomerulus
focal segmental glomerulosclerosis is the most common cause of nephrotic syndrome in which populations? [1]
African-Americans & Hispanics
Describe the pathophysiology of primary and secondary FSGS [2]
Primary FSGS: Idiopathic
- A circulating factor that damages podocytes in the glomeruli leading to foot process effacement
- Proteins and lipids pass through BUT ALSO get stuck inside th glomerulus causing hyalinosis and eventually sclerosis.
Secondary FSGS: SCA, post- HIV / Herion / Lithium
- represents an adaptive response to renal injury that is usually associated with less significant proteinuria and renal impairment.
Describe the clinical features of FSGS [4]
Nephrotic syndrome
Haematuria (microscopic)
Hypertension
Renal insufficiency
State 4 underlying conditions that produce secondary FSGS:
Viral [2]
Drug [3]
Other [2]
Viral infection:
- HIV
- CMV
Glomerular hyperfiltration:
- Due to reduced renal mass / solitary kidney etc
Drug induced:
- Heroin
- Interferon alpha
- Lithium
Obesity
What does renal biopsy depict in FSGS? [1]
Renal biopsy shows focal and segmental sclerosis and hyalinosis on light microscopy, and effacement of foot processes on electron microscopy. Sclerosis is seen in this light microscopy image next to the bowmans capsule.
Describe the management of FSGS [4]
Treat underlying cause
ACE inhibitor: enalapril or lisinopril to reduce proteinuria
Steroids; prednisolone (only in primary disease)
Furosemide
simvastatin / atorvostatin to control hyperlipidaemia
Define membranous nephropathy [1]
Membranous nephropathy (MN) is an immunologically mediated disease characterised by glomerular basement membrane thickening in the absence of significant cellular proliferation on histology
Describe the pathophysiology of membranous nephropathy [3]
Autoimmune reaction against important antigens in the filtration barrier.
This causes development of autoantibodies: directed against the phospholipase A2 receptor (PLA2R) that are highly expressed on podocytes are a major cause of primary MN seen in up to 80% of case
Causes the formation of immune deposits and subsequent thickening of the glomerular basement membrane.
Histology shows IgA deposits and mesangial proliferation.
Describe the biospy freatures of MN [3]
A thickened GBM with subepithelial electron-dense droplets.
This creates a ‘spike and dome’ appearance.
It is thought these subepithelial deposits are immunoglobulins, as it is primarily an autoimmune disease.
There will also be thickened capillary loops
Which pathology does a red cell cast indicate? [1]
Definitive of glomerulonephritis
Which pathology does a white cell cast indicate? [1]
Acute interstitial nephritis
Investigations for IgA nephropathy:
A diagnosis of IgAN can only be made by WHAT investigation? [1]
What are the results for this investigation? [1]
Kidney biopsy:
* Mesangial IgA deposition either by immunofluorescence or immunoperoxidase studies.
What does biopsy of kidneys of a patient with post-streptococcal glomerulonephritis depict? [2]
Subendothelial deposits activate complement, leading to the infiltration of inflammatory cells: neutrophils! and proliferative glomerulonephritits
Subepithelial ‘humps’ of deposits trigger inflammation, leading to epithelial cell damage, which allows the protein to filter more freely into the urine.
Describe what rapidly progressive glomerulonephritis is? [1]
How does it appear histologically ? [1]
Any aggressive GN, rapidly progressing to renal failure over days or weeks.
presents with an acute severe illness but tends to respond well to treatment.Histology shows glomerular crescents.
Describe what rapidly progressive glomerulonephritis is? [1]
How does it appear histologically ? [1]
